DOCSLIB.ORG

Cannabinoid Receptors and Pain

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Cannabinoid Receptors and Pain Progress in Neurobiology 63 (2001) 569–611 www.elsevier.com/locate/pneurobio Cannabinoid receptors and pain Roger G. Pertwee * Department of Biomedical Sciences, Institute of Medical Sciences, Uni6ersity of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, Scotland, UK Received 9 February 2000 Abstract Mammalian tissues contain at least two types of cannabinoid receptor, CB1 and CB2, both coupled to G proteins. CB1 receptors are expressed mainly by neurones of the central and peripheral nervous system whereas CB2 receptors occur centrally and peripherally in certain non-neuronal tissues, particularly in immune cells. The existence of endogenous ligands for cannabinoid receptors has also been demonstrated. The discovery of this ‘endocannabinoid system’ has prompted the development of a range of novel cannabinoid receptor agonists and antagonists, including several that show marked selectivity for CB1 or CB2 receptors. It has also been paralleled by a renewed interest in cannabinoid-induced antinociception. This review summarizes current knowledge about the ability of cannabinoids to produce antinociception in animal models of acute pain as well as about the ability of these drugs to suppress signs of tonic pain induced in animals by nerve damage or by the injection of an inflammatory agent. Particular attention is paid to the types of pain against which cannabinoids may be effective, the distribution pattern of cannabinoid receptors in central and peripheral pain pathways and the part that these receptors play in cannabinoid-induced antinociception. The possibility that antinociception can be mediated by cannabinoid receptors other than CB1 and CB2 receptors, for example CB2-like receptors, is also discussed as is the evidence firstly that one endogenous cannabinoid, anandamide, produces antinociception through mechanisms that differ from those of other types of cannabinoid, for example by acting on vanilloid receptors, and secondly that the endocannabinoid system has physiological and/or pathophysiological roles in the modulation of pain. © 2001 Elsevier Science Ltd. All rights reserved. Contents 1. Introduction ................................................ 570 1.1. The endocannabinoid system .................................. 570 1.2. Cannabinoid receptor ligands .................................. 572 2. Antinociceptive activity of cannabinoid receptor agonists...................... 573 2.1. Antinociception in acute pain models ............................. 574 2.2. Antinociception in tonic pain models ............................. 579 3. Antinociception and CB1 receptors ................................... 579 4. Antinociception and non-CB1 cannabinoid receptors ........................ 585 4.1. Non-CB1 cannabinoid receptors in the spinal cord...................... 585 4.2. Differences between cannabinoid receptor populations in brain and spinal cord..... 587 4.3. Different antinociceptive tests, different cannabinoid receptors? .............. 587 4.4. CB2 or CB2-like receptors .................................... 588 4.5. Novel ‘anandamide’ receptors.................................. 589 4.6. Anandamide and vanilloid receptors .............................. 590 * Tel.: +44-1224-273040; fax: +44-1224-273019. E-mail address: [email protected] (R.G. Pertwee). 0301-0082/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved. PII: S0301-0082(00)00031-9 570 R.G. Pertwee / Progress in Neurobiology 63 (2001) 569–611 5. Sites of action............................................... 591 5.1. Central sites of action ...................................... 591 5.2. Effects on descending control of spinal nociceptive neurones................ 593 5.3. Effects on primary afferent neurones ............................. 593 6. Cannabinoids and endogenous mediators of nociception or inflammation ............ 595 6.1. Excitatory and inhibitory amino acid transmitters ...................... 595 6.2. Peptides .............................................. 595 7. Mediators of cannabinoid-induced antinociception.......................... 596 7.1. Monoamine neurotransmitters ................................. 596 7.2. Opioid peptides .......................................... 596 8. Synergism between cannabinoids and opioids ............................ 598 9. Role of the endocannabinoid system in nociception ......................... 598 9.1. Effects of SR141716A on radiant heat or warm water tail flick responses in rats, mice and monkeys ........................................... 599 9.2. Effects of blocking agents on responses of unlesioned rodent paws to heat or mechanical pressure stimuli .......................................... 600 9.3. Effects of SR141716A and SR144528 in models of inflammatory pain .......... 600 9.4. Effect of SR141716A in a model of neuropathic pain .................... 601 9.5. Effects of SR141716A on nociceptive neurones........................ 601 9.6. Experiments with CB1 knockout mice ............................. 601 9.7. Endogenous cannabinoid production and nociception .................... 602 10. Summary and general discussion ................................... 602 References ................................................... 604 Nomenclature AM381 stearylsulphonyl fluoride AM404 N-(4-hydroxyphenyl)arachidonylamide i.a. intra-arterial cyclic cyclic 3%,5%-adenosine monophosphate i.c. intracerebral AMP i.c.v. intracerebroventricular CGRP calcitonin gene-related peptide i.pl. intraplantar (injection into plantar COX cyclo-oxygenase surface of paw) DAMGO [D-Ala2, N-Me-Phe4, Gly-ol5]-enkephalin i.t. intrathecal DMH dimethylheptyl KB equilibrium dissociation constant of a DPDPE [D-Pen2, D-Pen5]-enkephalin competitive reversible antagonist EC50 concentration eliciting a half-maximal Ki dissociation constant of an unlabelled response ligand as determined in a radioligand ED50 dose eliciting a half-maximal response competitive binding assay GABA g-aminobutyric acid NMDA N-methyl-D-aspartate HEK human embryonic kidney THC tetrahydrocannabinol 5-HT 5-Hydroxytryptamine (serotonin) HU-210 11-Hydroxy-dimethylheptyl-D8-tetra- hydrocannabinol 1. Introduction through Gi/o proteins, negatively to adenylate cyclase and positively to mitogen-activated protein kinase. In 1.1. The endocannabinoid system addition, CB1 receptors are coupled to ion channels through Gi/o proteins, positively to A-type and in- Two types of cannabinoid receptor have so far been wardly rectifying potassium channels and negatively to identified, CB1, cloned in 1990, and CB2, cloned in 1993 N-type and P/Q-type calcium channels and to D-type (Pertwee, 1997, 1998). Both receptor types are coupled potassium channels (Mu et al., 1999; Pertwee, 1997, R.G. Pertwee / Progress in Neurobiology 63 (2001) 569–611 571 1998). CB1 coupling to A-type and D-type potassium caudate-putamen, substantia nigra pars reticulata, channels is thought to be through adenylate cyclase globus pallidus, entopeduncular nucleus and cerebellum (Mu et al., 1999). CB1 receptors may also mobilize all contain significant numbers of CB1 receptors arachidonic acid and close 5-HT3 receptor ion channels (Pertwee, 1997, 1998). As discussed in section 5 of this (Pertwee, 1997) and, under certain conditions, activate review, CB1 receptors are also found in brain areas that adenylate cyclase through Gs proteins (Calandra et al., process or modulate nociceptive information. 1999; Glass and Felder, 1997). In addition, there are Some CB1 receptors are located at central and pe- ripheral nerve terminals (Ong and Mackie, 1999a; reports that CB1 receptors are negatively coupled to voltage-gated L-type calcium channels both in cat cere- Pertwee, 1997) where they probably modulate the re- bral arterial smooth muscle cells (Gebremedhin et al., lease of both excitatory and inhibitory neurotransmit- 1999) and in retinal bipolar cell axon terminals of larval ters when activated (Table 1; Kim and Thayer, 2000). It tiger salamanders (Straiker et al., 1999). Ho et al. would seem then that presynaptic CB1 receptors medi- (1999) have obtained evidence that inwardly rectifying ate mixed inhibitory-disinhibitory effects on neuro- potassium channels can serve as a signalling mechanism transmission through suppression of transmitter release whilst postsynaptic CB1 receptors, at least on for CB2 as well as CB1 receptors, at least in Xenopus oocytes that have been transfected with such channels hippocampal CA1 pyramidal neurones, are likely to have an excitatory effect on neurotransmission through together with CB1 or CB2 receptors. In other experi- ments, in which Xenopus oocytes were co-transfected their ability to close M-type potassium channels with cannabinoid receptors and certain G protein sub- (Schweitzer, 2000). units, this research group also obtained evidence that CB2 receptors occur mainly in immune cells where they may mediate an immunosuppressant effect CB1 but not CB2 receptors can activate phospholipase (Pertwee, 1997, 1998). Although CB2 mRNA has not C through G protein containing Ga ,Ga or Ga 14 15 16 been detected on neuronal tissue from human or rat subunits. Other recent findings are that CB receptors 1 brain (Munro et al., 1993; Galie`gue et al., 1995), there on hippocampal CA1 pyramidal neurones are nega- is evidence for its presence in rat brain microglia tively coupled to M-type potassium channels (Kearn and Hillard, 1999). There is also one report of (Schweitzer, 2000) and that CB receptors on cultured 1 the presence of CB mRNA together with CB mRNA cerebellar granule neurones can
Load more

Recommended publications
  • N-Acyl-Dopamines: Novel Synthetic CB1 Cannabinoid-Receptor Ligands
    Biochem. J. (2000) 351, 817–824 (Printed in Great Britain) 817 N-acyl-dopamines: novel synthetic CB1 cannabinoid-receptor ligands and inhibitors of anandamide inactivation with cannabimimetic activity in vitro and in vivo Tiziana BISOGNO*, Dominique MELCK*, Mikhail Yu. BOBROV†, Natalia M. GRETSKAYA†, Vladimir V. BEZUGLOV†, Luciano DE PETROCELLIS‡ and Vincenzo DI MARZO*1 *Istituto per la Chimica di Molecole di Interesse Biologico, C.N.R., Via Toiano 6, 80072 Arco Felice, Napoli, Italy, †Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, R. A. S., 16/10 Miklukho-Maklaya Str., 117871 Moscow GSP7, Russia, and ‡Istituto di Cibernetica, C.N.R., Via Toiano 6, 80072 Arco Felice, Napoli, Italy We reported previously that synthetic amides of polyunsaturated selectivity for the anandamide transporter over FAAH. AA-DA fatty acids with bioactive amines can result in substances that (0.1–10 µM) did not displace D1 and D2 dopamine-receptor interact with proteins of the endogenous cannabinoid system high-affinity ligands from rat brain membranes, thus suggesting (ECS). Here we synthesized a series of N-acyl-dopamines that this compound has little affinity for these receptors. AA-DA (NADAs) and studied their effects on the anandamide membrane was more potent and efficacious than anandamide as a CB" transporter, the anandamide amidohydrolase (fatty acid amide agonist, as assessed by measuring the stimulatory effect on intra- hydrolase, FAAH) and the two cannabinoid receptor subtypes, cellular Ca#+ mobilization in undifferentiated N18TG2 neuro- CB" and CB#. NADAs competitively inhibited FAAH from blastoma cells. This effect of AA-DA was counteracted by the l µ N18TG2 cells (IC&! 19–100 M), as well as the binding of the CB" antagonist SR141716A.
    [Show full text]
  • Opioids and Nicotine Dependence in Planarians
    Pharmacology, Biochemistry and Behavior 112 (2013) 9–14 Contents lists available at ScienceDirect Pharmacology, Biochemistry and Behavior journal homepage: www.elsevier.com/locate/pharmbiochembeh Opioid receptor types involved in the development of nicotine physical dependence in an invertebrate (Planaria)model Robert B. Raffa a,⁎, Steve Baron a,b, Jaspreet S. Bhandal a,b, Tevin Brown a,b,KevinSongb, Christopher S. Tallarida a,b, Scott M. Rawls b a Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA, USA b Department of Pharmacology & Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA, USA article info abstract Article history: Recent data suggest that opioid receptors are involved in the development of nicotine physical dependence Received 18 May 2013 in mammals. Evidence in support of a similar involvement in an invertebrate (Planaria) is presented using Received in revised form 18 September 2013 the selective opioid receptor antagonist naloxone, and the more receptor subtype-selective antagonists CTAP Accepted 21 September 2013 (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH )(μ, MOR), naltrindole (δ, DOR), and nor-BNI (norbinaltorphimine) Available online 29 September 2013 2 (κ, KOR). Induction of physical dependence was achieved by 60-min pre-exposure of planarians to nicotine and was quantified by abstinence-induced withdrawal (reduction in spontaneous locomotor activity). Known MOR Keywords: Nicotine and DOR subtype-selective opioid receptor antagonists attenuated the withdrawal, as did the non-selective Abstinence antagonist naloxone, but a KOR subtype-selective antagonist did not. An involvement of MOR and DOR, but Withdrawal not KOR, in the development of nicotine physical dependence or in abstinence-induced withdrawal was thus Physical dependence demonstrated in a sensitive and facile invertebrate model.
    [Show full text]
  • Efficacy of Cannabinoids in a Pre-Clinical Drug-Screening Platform for Alzheimer’S Disease
    Molecular Neurobiology https://doi.org/10.1007/s12035-019-1637-8 Efficacy of Cannabinoids in a Pre-Clinical Drug-Screening Platform for Alzheimer’s Disease David Schubert1 & Devin Kepchia1 & Zhibin Liang1 & Richard Dargusch1 & Joshua Goldberg & Pamela Maher1 Received: 30 January 2019 /Accepted: 6 May 2019 # Springer Science+Business Media, LLC, part of Springer Nature 2019 Abstract Finding a therapy for Alzheimer’s disease (AD) is perhaps the greatest challenge for modern medicine. The chemical scaffolds of many drugs in the clinic today are based upon natural products from plants, yet Cannabis has not been extensively examined as a source of potential AD drug candidates. Here, we determine if a number of non-psychoactive cannabinoids are neuroprotective in a novel pre-clinical AD and neurodegeneration drug-screening platform that is based upon toxicities associated with the aging brain. This drug discovery paradigm has yielded several compounds in or approaching clinical trials for AD. Eleven cannabinoids were assayed for neuroprotection in assays that recapitulate proteotoxicity, loss of trophic support, oxidative stress, energy loss, and inflammation. These compounds were also assayed for their ability to remove intraneuronal amyloid and subjected to a structure-activity relationship analysis. Pairwise combinations were assayed for their ability to synergize to produce neuropro- tective effects that were greater than additive. Nine of the 11 cannabinoids have the ability to protect cells in four distinct phenotypic neurodegeneration screening assays, including those using neurons that lack CB1 and CB2 receptors. They are able to remove intraneuronal Aβ, reduce oxidative damage, and protect from the loss of energy or trophic support.
    [Show full text]
  • Endocannabinoid System Dysregulation from Acetaminophen Use May Lead to Autism Spectrum Disorder: Could Cannabinoid Treatment Be Efficacious?
    molecules Review Endocannabinoid System Dysregulation from Acetaminophen Use May Lead to Autism Spectrum Disorder: Could Cannabinoid Treatment Be Efficacious? Stephen Schultz 1, Georgianna G. Gould 1, Nicola Antonucci 2, Anna Lisa Brigida 3 and Dario Siniscalco 4,* 1 Department of Cellular and Integrative Physiology, Center for Biomedical Neuroscience, University of Texas (UT) Health Science Center San Antonio, San Antonio, TX 78229, USA; [email protected] (S.S.); [email protected] (G.G.G.) 2 Biomedical Centre for Autism Research and Therapy, 70126 Bari, Italy; [email protected] 3 Department of Precision Medicine, University of Campania, 80138 Naples, Italy; [email protected] 4 Department of Experimental Medicine, University of Campania, 80138 Naples, Italy * Correspondence: [email protected] Abstract: Persistent deficits in social communication and interaction, and restricted, repetitive pat- terns of behavior, interests or activities, are the core items characterizing autism spectrum disorder (ASD). Strong inflammation states have been reported to be associated with ASD. The endocannabi- noid system (ECS) may be involved in ASD pathophysiology. This complex network of lipid signal- ing pathways comprises arachidonic acid and 2-arachidonoyl glycerol-derived compounds, their G-protein-coupled receptors (cannabinoid receptors CB1 and CB2) and the associated enzymes. Alter- Citation: Schultz, S.; Gould, G.G.; ations of the ECS have been reported in both the brain and the immune system of ASD subjects. ASD Antonucci, N.; Brigida, A.L.; Siniscalco, D. Endocannabinoid children show low EC tone as indicated by low blood levels of endocannabinoids. Acetaminophen System Dysregulation from use has been reported to be associated with an increased risk of ASD.
    [Show full text]
  • The Complex Pharmacology of Cannabis Ben J
    The complex pharmacology of cannabis Ben J. Whalley [email protected] 28 June 2013 © University of Reading 2009 www.reading.ac.uk/cinn Outline • Constituents of cannabis – Cannabinoids and non-cannabinoids – Historical changes in composition • The endocannabinoid system – The physiological system affected by THC – Dispelling myths aka ‘Just because it has ‘cannab’ in the name…’ – Cannabinoids that do act via the endocannabinoid system • Beyond the endocannabinoid system – Cannabinoids that don’t act via the endocannabinoid system • Considerations for human medical development and use – Modulating the ubiquitous – Natural ≠ safe – Winning strategies: ‘Smaller & Quicker’ or ‘Slower & Larger’? [email protected] 2 Constituents of cannabis • Cannabis: for the most part, we are talking about the plant Cannabis sativa. • You’ve probably gathered that it one of the most widely used recreational and medicinal drugs worldwide. – ~150 million people smoking cannabis daily (WHO) • May be the first non-food plant cultivated by humans (~8000 BC)[2]. • Best known for its psychoactive constituent, Δ9- tetrahydrocannabinol (‘THC’). [email protected] Much, much more than just D9-THC • In addition to D9-THC, cannabis also contains: • >100 other ‘cannabinoids’ – Cannabinoids are chemical entities that are structurally similar to THC[3]. – phenol ring, 5-carbon alkyl chain, central pyran ring and mono- unsaturated cyclohexyl ring. – Not found in any other plant. • >400 other non-cannabinoids[3]. – Cannot rule out specific effects of
    [Show full text]
  • Kappa Opioid Regulation of Depressive-Like Behavior During Acute Withdrawal and Protracted Abstinence from Ethanol Sorscha K
    Grand Valley State University ScholarWorks@GVSU Funded Articles Open Access Publishing Support Fund 9-2018 Kappa Opioid Regulation of Depressive-Like Behavior During Acute Withdrawal and Protracted Abstinence from Ethanol Sorscha K. Jarman Grand Valley State University, [email protected] Alison M. Haney Grand Valley State University, [email protected] Glenn R. Valdez Grand Valley State University, [email protected] Follow this and additional works at: https://scholarworks.gvsu.edu/oapsf_articles Part of the Chemicals and Drugs Commons ScholarWorks Citation Jarman, Sorscha K.; Haney, Alison M.; and Valdez, Glenn R., "Kappa Opioid Regulation of Depressive-Like Behavior During Acute Withdrawal and Protracted Abstinence from Ethanol" (2018). Funded Articles. 106. https://scholarworks.gvsu.edu/oapsf_articles/106 This Article is brought to you for free and open access by the Open Access Publishing Support Fund at ScholarWorks@GVSU. It has been accepted for inclusion in Funded Articles by an authorized administrator of ScholarWorks@GVSU. For more information, please contact [email protected]. RESEARCH ARTICLE Kappa opioid regulation of depressive-like behavior during acute withdrawal and protracted abstinence from ethanol ¤ Sorscha K. Jarman, Alison M. Haney , Glenn R. ValdezID* Department of Psychology, Grand Valley State University, Allendale, MI, United States of America ¤ Current address: Department of Psychology, Purdue University, West Lafayette, IN, United States of America * [email protected] a1111111111 a1111111111 a1111111111 a1111111111 Abstract a1111111111 The dynorphin/kappa opioid receptor (DYN/KOR) system appears to be a key mediator of the behavioral effects of chronic exposure to alcohol. Although KOR opioid receptor antago- nists have been shown to decrease stress-related behaviors in animal models during acute ethanol withdrawal, the role of the DYN/KOR system in regulating long-term behavioral OPEN ACCESS changes following protracted abstinence from ethanol is not well understood.
    [Show full text]
  • Datasheet Inhibitors / Agonists / Screening Libraries a DRUG SCREENING EXPERT
    Datasheet Inhibitors / Agonists / Screening Libraries A DRUG SCREENING EXPERT Product Name : Norbinaltorphimine dihydrochloride Catalog Number : T12241 CAS Number : 113158-34-2 Molecular Formula : C40H45Cl2N3O6 Molecular Weight : 734.71 Description: Norbinaltorphimine dihydrochloride is a potent and selective antagonist of κ opioid receptor. Storage: 2 years -80°C in solvent; 3 years -20°C powder; Receptor (IC50) κ opioid receptor In vivo Activity The KOR antagonist, Norbinaltorphimine(norBNI), had weak and inconsistent effects on THC-induced taste avoidance in adolescent rats in that norBNI both attenuated and strengthened taste avoidance dependent on dose and trial. norBNI had limited impact on the final one-bottle avoidance and no effects on the two-bottle preference test. Interestingly, norBNI had no effect on THC-induced taste avoidance in adult rats as well. Reference 1. Flax SM, et al. Effect of norbinaltorphimine on ∆⁹-tetrahydrocannabinol (THC)-induced taste avoidance in adolescent and adult Sprague-Dawley rats. Psychopharmacology (Berl). 2015 Sep;232(17):3193-201. 2. Jackson KJ, et al. Effects of the kappa opioid receptor antagonist, norbinaltorphimine, on stress and drug-induced reinstatement of nicotine-conditioned place preference in mice. Psychopharmacology (Berl). 2013 Apr;226(4):763-8. FOR RESEARCH PURPOSES ONLY. NOT FOR DIAGNOSTIC OR THERAPEUTIC USE. Information for product storage and handling is indicated on the product datasheet. Targetmol products are stable for long term under the recommended storage conditions. Our products may be shipped under different conditions as many of them are stable in the short-term at higher or even room temperatures. We ensure that the product is shipped under conditions that will maintain the quality of the reagents.
    [Show full text]
  • Appendix-2Final.Pdf 663.7 KB
    North West ‘Through the Gate Substance Misuse Services’ Drug Testing Project Appendix 2 – Analytical methodologies Overview Urine samples were analysed using three methodologies. The first methodology (General Screen) was designed to cover a wide range of analytes (drugs) and was used for all analytes other than the synthetic cannabinoid receptor agonists (SCRAs). The analyte coverage included a broad range of commonly prescribed drugs including over the counter medications, commonly misused drugs and metabolites of many of the compounds too. This approach provided a very powerful drug screening tool to investigate drug use/misuse before and whilst in prison. The second methodology (SCRA Screen) was specifically designed for SCRAs and targets only those compounds. This was a very sensitive methodology with a method capability of sub 100pg/ml for over 600 SCRAs and their metabolites. Both methodologies utilised full scan high resolution accurate mass LCMS technologies that allowed a non-targeted approach to data acquisition and the ability to retrospectively review data. The non-targeted approach to data acquisition effectively means that the analyte coverage of the data acquisition was unlimited. The only limiting factors were related to the chemical nature of the analyte being looked for. The analyte must extract in the sample preparation process; it must chromatograph and it must ionise under the conditions used by the mass spectrometer interface. The final limiting factor was presence in the data processing database. The subsequent study of negative MDT samples across the North West and London and the South East used a GCMS methodology for anabolic steroids in addition to the General and SCRA screens.
    [Show full text]
  • NIDA Drug Supply Program Catalog, 25Th Edition
    RESEARCH RESOURCES DRUG SUPPLY PROGRAM CATALOG 25TH EDITION MAY 2016 CHEMISTRY AND PHARMACEUTICS BRANCH DIVISION OF THERAPEUTICS AND MEDICAL CONSEQUENCES NATIONAL INSTITUTE ON DRUG ABUSE NATIONAL INSTITUTES OF HEALTH DEPARTMENT OF HEALTH AND HUMAN SERVICES 6001 EXECUTIVE BOULEVARD ROCKVILLE, MARYLAND 20852 160524 On the cover: CPK rendering of nalfurafine. TABLE OF CONTENTS A. Introduction ................................................................................................1 B. NIDA Drug Supply Program (DSP) Ordering Guidelines ..........................3 C. Drug Request Checklist .............................................................................8 D. Sample DEA Order Form 222 ....................................................................9 E. Supply & Analysis of Standard Solutions of Δ9-THC ..............................10 F. Alternate Sources for Peptides ...............................................................11 G. Instructions for Analytical Services .........................................................12 H. X-Ray Diffraction Analysis of Compounds .............................................13 I. Nicotine Research Cigarettes Drug Supply Program .............................16 J. Ordering Guidelines for Nicotine Research Cigarettes (NRCs)..............18 K. Ordering Guidelines for Marijuana and Marijuana Cigarettes ................21 L. Important Addresses, Telephone & Fax Numbers ..................................24 M. Available Drugs, Compounds, and Dosage Forms ..............................25
    [Show full text]
  • Abstract Book 2012.Indd
    SUPPLEMENT TO JOURNAL OF PSYCHOPHARMACOLOGY VOL 26, SUPPLEMENT TO ISSUE 8, AUGUST 2012 These papers were presented at the Summer Meeting of the BRITISH ASSOCIATION FOR PSYCHOPHARMACOLOGY 22 – 25 July, Harrogate, UK Indemnity The scientific material presented at this meeting reflects the opinions of the contributing authors and speakers. The British Association for Psychopharmacology accepts no responsibility for the contents of the verbal or any published proceedings of this meeting. BAP OFFICE 36 Cambridge Place Hills Road Cambridge CB2 1NS bap.org.uk Aii CONTENTS Abstract Book 2012 Abstracts begin on page: SYMPOSIUM 1 A1 Drugs as tools in neuropsychiatry: Ketamine (S01-S04) SYMPOSIUM 2 A2 New tricks for old drugs: Opiates, addiction and beyond (S05-S08) SYMPOSIUM 3 A3 Advances in understanding brain corticosteroid responses to stress: relevance to depression (S09-S12) SYMPOSIUM 4 A5 Cognitive impairment in depression: A target for treatment? (S13-S16) SYMPOSIUM 5 A6 New treatment strategies for targeting drug addictions – A translational perspective (S17-S20) SYMPOSIUM 6 A7 Functional imaging markers for monitoring treatment: Mechanisms and efficacy (S21-S24) SYMPOSIUM 7 A9 Schizophrenia Treatment: What’s wrong with it and what might work better (S25-S28) SYMPOSIUM 8 A10 Epigenetics and psychiatry - current understanding and therapeutic potential (S29-S32) SYMPOSIUM 9 A11 Rethinking the compulsive aspects of addiction: From bench to bedside (S33-S36) POSTERS Anxiety 1 (MA01-MA07) A13 Affective Disorders 1 (MB01-MB20) A16 Brain Imaging
    [Show full text]
  • Marrakesh Agreement Establishing the World Trade Organization
    No. 31874 Multilateral Marrakesh Agreement establishing the World Trade Organ ization (with final act, annexes and protocol). Concluded at Marrakesh on 15 April 1994 Authentic texts: English, French and Spanish. Registered by the Director-General of the World Trade Organization, acting on behalf of the Parties, on 1 June 1995. Multilat ral Accord de Marrakech instituant l©Organisation mondiale du commerce (avec acte final, annexes et protocole). Conclu Marrakech le 15 avril 1994 Textes authentiques : anglais, français et espagnol. Enregistré par le Directeur général de l'Organisation mondiale du com merce, agissant au nom des Parties, le 1er juin 1995. Vol. 1867, 1-31874 4_________United Nations — Treaty Series • Nations Unies — Recueil des Traités 1995 Table of contents Table des matières Indice [Volume 1867] FINAL ACT EMBODYING THE RESULTS OF THE URUGUAY ROUND OF MULTILATERAL TRADE NEGOTIATIONS ACTE FINAL REPRENANT LES RESULTATS DES NEGOCIATIONS COMMERCIALES MULTILATERALES DU CYCLE D©URUGUAY ACTA FINAL EN QUE SE INCORPOR N LOS RESULTADOS DE LA RONDA URUGUAY DE NEGOCIACIONES COMERCIALES MULTILATERALES SIGNATURES - SIGNATURES - FIRMAS MINISTERIAL DECISIONS, DECLARATIONS AND UNDERSTANDING DECISIONS, DECLARATIONS ET MEMORANDUM D©ACCORD MINISTERIELS DECISIONES, DECLARACIONES Y ENTEND MIENTO MINISTERIALES MARRAKESH AGREEMENT ESTABLISHING THE WORLD TRADE ORGANIZATION ACCORD DE MARRAKECH INSTITUANT L©ORGANISATION MONDIALE DU COMMERCE ACUERDO DE MARRAKECH POR EL QUE SE ESTABLECE LA ORGANIZACI N MUND1AL DEL COMERCIO ANNEX 1 ANNEXE 1 ANEXO 1 ANNEX
    [Show full text]
  • Risk Assessment Report on a New Psychoactive Substance: N-Phenyl- N-[1-(2-Phenylethyl)Piperidin-4-Yl]Furan-2-Carboxamide (Furanylfentanyl)
    This document is being made available in advance of formal layout. It will be replaced with a final version in the formal EMCDDA layout in due course. Risk assessment report on a new psychoactive substance: N-phenyl- N-[1-(2-phenylethyl)piperidin-4-yl]furan-2-carboxamide (furanylfentanyl) In accordance with Article 6 of Council Decision 2005/387/JHA on the information exchange, risk assessment and control of new psychoactive substances Risk assessment report on a new psychoactive substance: N- phenyl -N -[1-(2-phenylethyl)piperidin-4-yl]furan-2-carboxamide (furanylfentanyl) In accordance with Article 6 of Council Decision 2005/387/JHA on the information exchange, risk assessment and control of new psychoactive substances Contents 1. Introduction ........................................................................................................................ 3 2. Physical, chemical and pharmacological description .......................................................... 5 3. Chemical precursors that are used for the manufacture ................................................... 10 4. Health risks ...................................................................................................................... 11 5. Social risks ...................................................................................................................... 18 6. Information on manufacturing, trafficking, distribution, and the level of involvement of organised crime ..............................................................................................................
    [Show full text]